Water → 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-4-(tetrahydro-2H-pyran-2-yloxy)-2-butyn-1-ol

HRID 1373796ノート

反応式

HRID 1373796 の反応式
[CH2:1]([O:4][CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][O:6]1)[C:2]#[CH:3].C([Li])CCC.[Cl:16][C:17]1[N:22]2[N:23]=[C:24]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[C:25]([CH:26]=[O:27])=[C:21]2[CH:20]=[CH:19][CH:18]=1.O>O1CCCC1.CCOCC>[Cl:16][C:17]1[N:22]2[N:23]=[C:24]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[C:25]([CH:26]([OH:27])[C:3]#[C:2][CH2:1][O:4][CH:5]3[CH2:10][CH2:9][CH2:8][CH2:7][O:6]3)=[C:21]2[CH:20]=[CH:19][CH:18]=1

参加物

7

反応物 4

HCID 962WaterHCID 98609Tetrahydro-2-(2-propynyloxy)-2H-pyranHCID 221748437-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-3-carbaldehydeHCID 178418339Butyllithium

生成物 1

HCID 866168561-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-4-(tetrahydro-2H-pyran-2-yloxy)-2-butyn-1-ol収率 99.4%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To a cold (−78° C.) solution of tetrahydro-2-(2-propynyloxy)-2H-pyran (0.5 mL, 3.6 mmol) in tetrahydrofuran (10 mL) was added n-butyllithium (2.05 mL, 1.6 M in hexanes, 3.3 mmol) dropwise. The reaction mixture was allowed to warm to 0° C., then cooled to −78° C. A separate solution of 7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridine-3-carbaldehyde (200 mg, 0.73 mmol) in tetrahydrofuran (5 mL) was cooled to 0° C. The alkynyllithium solution was added to the aldehyde solution via canula. The reaction mixture was allowed to warm to room temperature and stirred for 1 hour. Water was added followed by ether. The organic layer was washed with water and brine. The aqueous layer was extracted with ether and the combined organics were dried over magnesium sulfate. Filtration and concentration followed by flash chromatography (2:1 hexanes:ethyl acetate) provided 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]-4-(tetrahydro-2H-pyran-2-yloxy)-2-butyn-1-ol (301 mg, 99%) as a mixture of diastereomers. 1H NMR (CDCl3) δ 8.00 (d, 1H), 7.79 (m, 2H), 7.17 (m 3H), 6.99 (m, 1H), 5.79 (s, 1H), 4.81–4.74 (m, 1H), 4.39–4.25 (m, 2H), 3.81 (m, 1H), 3.52 (m, 1H), 3.15 (broad, 1H), 1.90–1.48 (m, 6H); 19F NMR (CDCl3) δ −113.01; MS m/z 437 (M+Na+).

後処理

  1. temperaturecooled to −78° C
  2. temperatureto warm to room temperature
  3. washThe organic layer was washed with water and brine
  4. extractionThe aqueous layer was extracted with ether
  5. dry with materialthe combined organics were dried over magnesium sulfate
  6. filtrationFiltration and concentration

出典と根拠

ORDレコード
ord-e22493f176a84c758501a2956435ebc8
出典データセット
uspto-grants-2007_01
特許番号
US07163940B2

反応ノート

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